Change search
ReferencesLink to record
Permanent link

Direct link
Premature proliferative arrest of cricopharyngeal myoblasts in oculo-pharyngeal muscular dystrophy: Therapeutic perspectives of autologous myoblast transplantation.
Show others and affiliations
2006 (English)In: Neuromuscular Disorders, ISSN 0960-8966, Vol. 16, no 11, 770-81 p.Article in journal (Refereed) Published
Abstract [en]

Cultures of myoblasts isolated from cricopharyngeal muscles from patients with oculopharyngeal muscular dystrophy (OPMD) have been performed to study the effect of the expanded (GCG)8-13 repeat, located on the poly(A) binding protein nuclear-1 (PABPN1), on satellite cell phenotype. Cell cultures exhibited a reduced myogenicity, as well as a rapid decrease in proliferative lifespan, as compared to controls. The incorporation of BrdU decreased during the proliferative lifespan, due to a progressive accumulation of non-dividing cells. A lower fusion index was also observed, but myoblasts were able to form large myotubes when OPMD cultures were purified, although a rapid loss of myogenicity during successive passages was also observed. Myoblasts isolated from unaffected muscles did not show the defects observed in cricopharyngeal muscle cultures. The PABPN1 was predominantly located in nuclei of myoblasts and in both the nuclei and cytoplasm of myotubes in OPMD cultures. In vivo analysis of OPMD muscles showed that the number of satellite cells was slightly higher than that observed in age matched controls. Mutation of the PABPN1 in OPMD provokes premature senescence in dividing myoblasts, that may be due to intranuclear toxic aggregates. These results suggest that myoblast autografts, isolated from unaffected muscles, and injected into the dystrophic pharyngeal muscles, may be a useful therapeutic strategy to restore muscular function. Its tolerance and feasibility has been preclinically demonstrated in the dog.

Place, publisher, year, edition, pages
2006. Vol. 16, no 11, 770-81 p.
Keyword [en]
Adult, Aged, Aged; 80 and over, Animals, Biopsy, Cell Aging, Cell Proliferation, Cell Transplantation/methods, Cells; Cultured, DNA/metabolism, Dogs, Esophageal Sphincter; Upper/*pathology, Gene Expression Regulation/genetics, Humans, Middle Aged, Muscular Dystrophy; Oculopharyngeal/genetics/metabolism/*pathology/*therapy, Myoblasts/metabolism/pathology/*transplantation, Phenotype, Poly(A)-Binding Protein II/*genetics/metabolism, Satellite Cells; Skeletal Muscle/pathology, Transplantation; Autologous, Trinucleotide Repeats
URN: urn:nbn:se:umu:diva-12684DOI: doi:10.1016/j.nmd.2006.07.022PubMedID: 17005403OAI: diva2:152355
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2011-01-11Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Thornell, Lars-Eric
By organisation

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 23 hits
ReferencesLink to record
Permanent link

Direct link